In-vitro cytotoxicity of synthesized phthalide-fused indoles and indolines against HL-60 and HepG2 cells

Abstract

Phthalide derivatives bearing indole or indoline moieties were successfully synthesized via eco-friendly method and were evaluated for their antiproliferative activity on HL-60 and HepG2 cell lines in vitro. At a final concentration of 100 μM, most of the compounds showed moderate potency on both the cell lines tested. Compound 3b bearing 5-chloro substituted indoline had the best potency against HL-60 and HepG2 cell lines with IC50 values of 45.4 and 57.7 μM, respectively. It was also found that replacement of a conjugated indoline to indole moiety gave better antiproliferative activity on HL-60 cells by almost two-fold. Morphological observation demonstrated numerous fragmented nuclei which are indicative of apoptosis. Molecular docking studies predicted non-covalent interactions and H-bonding of selected compounds with the P2 binding hot spot of the anti-apoptotic protein, Bcl-2, formed by Asp108, Phe109, Met112, Leu134, Arg143, Ala146 and Val153. Overall, our work highlights the potential of synthesized phthalide-fused indoles or indolines as antitumor agents. Keywords: Phthalide, Indole, Indoline, Antiproliferative activity, Molecular docking